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December 2, 2014 u vol. 111 u no. 48 u 16975–17336 Cover image: Pictured is a vermillion sea star, Mediaster aequalis,inPorlierPass,British Columbia, that shows signs of sea-star wasting disease. As of June 2014, the disease had affected 20 species of sea stars from Alaska to Baja California, but its cause is unknown. Ian Hewson et al. surveyed sea-star populations and conducted laboratory infection studies. They found that sea-star wasting disease is likely caused by a virus and identified a densovirus as a potential infectious agent. See the article by Hewson et al. on pages 17278–17283. Image courtesy of Peter Luckham (www.divemaster.ca). From the Cover 17278 Potential cause of sea-star wasting disease 17075 Human ability to evaluate probabilities 17122 X-ray free crystallography 17140 DNA binding site recognition by regulatory proteins 17182 Ebola antibodies’ modes of action Contents COMMENTARIES 16982 Going viral and the fatal vulnerability of neurons from immunity, not from infection THIS WEEK IN PNAS Lawrence Steinman See companion article on page 16053 in issue 45 of volume 111 16975 In This Issue 16984 Fuzzy universality of probability judgment Valerie F. Reyna and Charles J. Brainerd See companion article on page 17075 INNER WORKINGS—An over-the-shoulder look at scientists at work 16986 Expanding the femtosecond crystallography toolkit Sol M. Gruner 16977 Inner Workings: Freeing the dinos within See companion article on page 17122 Stephen Ornes CORE CONCEPTS—A brief introduction to emerging topics in science PNAS PLUS 16978 Core Concept: Synthetic biology—change, accelerated 16988 Significance Statements Danielle Venton Brief statements written by the authors about the significance of their papers. -
Hria Medical Foundation 2012 Review
20․12 DI VISION REVIE W Where Science and Philanthropy Converge IN THIS ISSUE: About Us and Our Services / 2 Funding Opportunities Jeffress Trust /8 Hood Foundation /10 Noonan Memorial Research Fund /11 Klarman Family Foundation /12 King Trust /13 Thome Foundation /14 Smith Family Foundation /16 Davis Foundation /17 Lymphatic Research Foundation /18 Scientific Review Committees /19 Gene Discovery in Anorexia Nervosa / 6 The Medical Foundation, a division of HRiA About Us Since 1957, foundations, bank trusts and individuals have engaged us to create and manage customized biomedical research grant programs that accelerate the pace of scientific discoveries. As evidenced by the more than 145,000 visits to our website this year alone, our funding announcements reach thousands of potential applicants for every grant cycle. And, by building a distinguished Scientific Review Committee for each program, we ensure critical and unbiased selection of the best minds in science. In 2012, we were privileged to work with foundations and bank trust departments whose grant programs distributed more than $18 million to investigators and physician-scientists across the United States and worldwide. Sally E. McNagny, M.D., M.P.H., F.A.C.P., Vice President Since 2001, Dr. McNagny has served as Vice President and head of HRiA’s Medical Foundation division where she leads biomedical research grantmaking and life sciences consulting. Dr. McNagny also serves on the faculty at Harvard Medical School and is a Fellow of the American College of Physicians. She holds a B.S. in Biology from Stanford University, an M.D. from Harvard Medical School, an M.P.H. -
Medical Advisory Board September 1, 2006–August 31, 2007
hoWard hughes medical iNstitute 2007 annual report What’s Next h o W ard hughes medical i 4000 oNes Bridge road chevy chase, marylaNd 20815-6789 www.hhmi.org N stitute 2007 a nn ual report What’s Next Letter from the president 2 The primary purpose and objective of the conversation: wiLLiam r. Lummis 6 Howard Hughes Medical Institute shall be the promotion of human knowledge within the CREDITS thiNkiNg field of the basic sciences (principally the field of like medical research and education) and the a scieNtist 8 effective application thereof for the benefit of mankind. Page 1 Page 25 Page 43 Page 50 seeiNg Illustration by Riccardo Vecchio Südhof: Paul Fetters; Fuchs: Janelia Farm lab: © Photography Neurotoxin (Brunger & Chapman): Page 3 Matthew Septimus; SCNT images: by Brad Feinknopf; First level of Rongsheng Jin and Axel Brunger; iN Bruce Weller Blake Porch and Chris Vargas/HHMI lab building: © Photography by Shadlen: Paul Fetters; Mouse Page 6 Page 26 Brad Feinknopf (Tsai): Li-Huei Tsai; Zoghbi: Agapito NeW Illustration by Riccardo Vecchio Arabidopsis: Laboratory of Joanne Page 44 Sanchez/Baylor College 14 Page 8 Chory; Chory: Courtesy of Salk Janelia Farm guest housing: © Jeff Page 51 Ways Illustration by Riccardo Vecchio Institute Goldberg/Esto; Dudman: Matthew Szostak: Mark Wilson; Evans: Fred Page 10 Page 27 Septimus; Lee: Oliver Wien; Greaves/PR Newswire, © HHMI; Mello: Erika Larsen; Hannon: Zack Rosenthal: Paul Fetters; Students: Leonardo: Paul Fetters; Riddiford: Steitz: Harold Shapiro; Lefkowitz: capacity Seckler/AP, © HHMI; Lowe: Zack Paul Fetters; Map: Reprinted by Paul Fetters; Truman: Paul Fetters Stewart Waller/PR Newswire, Seckler/AP, © HHMI permission from Macmillan Page 46 © HHMI for Page 12 Publishers, Ltd.: Nature vol. -
Prion Diseases in Knock-In Mice Carrying Single Prp Codon Substitutions Associated with Human Diseases
Profoundly different prion diseases in knock-in mice carrying single PrP codon substitutions associated with human diseases Walker S. Jacksona,b,c,1, Andrew W. Borkowskia,b,c, Nicki E. Watsona, Oliver D. Kingd, Henryk Faase, Alan Jasanoffe,f, and Susan Lindquista,b,c,2 aWhitehead Institute for Biomedical Research, Cambridge, MA 02142; bHoward Hughes Medical Institute, cDepartment of Biology, and fDepartments of Biological Engineering, Brain and Cognitive Sciences, and Nuclear Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; dDepartment of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01655; and eFrances Bitter Magnet Laboratory, Cambridge, MA 02139 Contributed by Susan Lindquist, July 9, 2013 (sent for review March 7, 2013) In man, mutations in different regions of the prion protein (PrP) linked to it, provides an important general model for such are associated with infectious neurodegenerative diseases that investigations. have remarkably different clinical signs and neuropathological There are several types of human prion diseases, each begin- lesions. To explore the roots of this phenomenon, we created ning with pathologic processes in a different brain region and fi – a knock-in mouse model carrying the mutation associated with leading to distinct functional de cits: cognition [Creutzfeldt – – one of these diseases [Creutzfeldt–Jakob disease (CJD)] that was Jakob disease (CJD)], movement control (Gerstmann Sträussler Scheinker syndrome), or sleep and autonomic functions [fatal exactly analogous to a previous knock-in model of a different fl prion disease [fatal familial insomnia (FFI)]. Together with the familial insomnia (FFI)] (7). Prion diseases also af ict animals WT parent, this created an allelic series of three lines, each express- and include bovine spongiform encephalopathy (BSE) of cattle, scrapie of sheep and goats, and chronic wasting disease (CWD) ing the same protein with a single amino acid difference, and with of deer and elk (1). -
Susan Lee Lindquist (1949–2016)
In Memoriam Sue was a spectacular scientist who com- at the University of Chicago, where she bined a searing intellect with deep wis- would later join the faculty (1978) and rise Susan Lee Lindquist (1949–2016) dom, sagacious intuition, and limitless to full professor (1988). While at the Uni- creativity. These characteristics enabled versity of Chicago, Sue married Edward Sue to make connections across dispa- Buckbee and would have two wonderful 1, James Shorter * rate disciplines that nobody else could daughters, Alana and Nora. She also make. Her infectious esprit for scientific launched a remarkable and radical series Lindquist was a visionary and pio- discovery was combined with disarming of trailblazing discoveries. These contin- neer who transformed our under- warmth, positivity, openness, directness, ued when Sue moved her research pro- standing of how protein folding and generosity, which made her an inspi- gram to the Whitehead Institute for rational, nurturing, and indefatigable men- Biomedical Research at Massachusetts sculpts biology, evolution, and dis- tor. These synergistic traits empowered Institute of Technology (MIT), which is ease. She revealed several unantici- extraordinarily effective collaborations where I trained with Sue as a postdoctoral pated mechanisms by which protein between scientists from diverse back- fellow (2002–2007). Sue would spend the folding can buffer, release, and grounds and disciplines. Indeed, rest of her career at the Whitehead Insti- potentiate genetic variation in researchers from diverse backgrounds – tute as Director (2001–2004), Institute response to environmental stress, physicists, chemists, biochemists, biolo- Member (2001–2016), and Professor of thereby enabling the rapid evolution gists, mathematicians, and physicians – Biology at MIT (2001–2016). -
Calcineurin Determines Toxic Versus Beneficial Responses to Α-Synuclein
Calcineurin determines toxic versus beneficial responses to α-synuclein Gabriela Caraveoa,b, Pavan K. Aulucka,c,1, Luke Whitesella, Chee Yeun Chunga, Valeriya Barua,b, Eugene V. Mosharovd, Xiaohui Yane, Manu Ben-Johnyf, Martin Sosteg, Paola Picottig, Hanna Kime, Kim A. Caldwelle, Guy A. Caldwelle, David Sulzerd,h, David T. Yuef, and Susan Lindquista,b,2 aWhitehead Institute for Biomedical Research, Cambridge, MA 02142; bHoward Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139; cDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114; Departments of dNeurology and hPsychiatry, Columbia University Medical Center, New York, NY 10032; eDepartment of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487; fDepartments of Biomedical Engineering and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; and gDepartment of Biology, Institute of Biochemistry, Eidgenossische Technische Hochschule Zurich, Zurich CH-8093, Switzerland Contributed by Susan Lindquist, July 15, 2014 (sent for review May 7, 2014) + Calcineurin (CN) is a highly conserved Ca2 –calmodulin (CaM)- tigations, given their genetic tractability and the remarkable + + dependent phosphatase that senses Ca2 concentrations and trans- conservation of Ca2 -signaling pathways from yeast to humans duces that information into cellular responses. Ca2+ homeostasis (14, 15). Moreover, the expression of human α-syn in yeast leads is disrupted by α-synuclein (α-syn), a small lipid binding protein to cellular pathologies directly relevant to neurons and PD, in- whose misfolding and accumulation is a pathological hallmark of cluding nitrosative stress (16, 17), defects in vesicle trafficking several neurodegenerative diseases. We report that α-syn, from (18–20), and faulty mitochondrial function (21, 22). -
Division of Extramural Activities Annual Report 2002
Division of Extramural Activities Annual Report 2002 National Institutes of Health National Cancer Institute Molecular Diagnosis of Cancer Gene expression profiling using DNA microarrays is a technology that arose as a consequence of the Human Genome Project. With DNA microarrays, it is possible to determine the activity (“expression”) of tens of thousands of genes in parallel on microarray plates. The expression of genes influences the biological behavior of a cell because it dictates which proteins the cell can make and gives cells their unique characteristics. In the DNA microarray images shown at the bottom of the cover illustration, each spot represents a different human gene. Red, yellow, and green spots indicate that a gene is expressed at high, intermediate, and low levels, respectively. The pattern of expression of all of the genes in a cell constitutes its gene expression “profile.” Using DNA microarrays, different types of normal and malignant cells can be distinguished from one another because they have distinct gene expression profiles. Shown at the top of the cover illustration are photomicrographs of lymph node biopsies from two patients with diffuse large B cell lymphoma. The tumor at the right belongs to the germinal center B cell-like subgroup of diffuse large B cell lymphoma. Patients with this lymphoma type have a relatively favorable 5-year survival rate of 59% following multi-agent chemotherapy. The tumor at the left belongs to the activated B cell-like subgroup of diffuse large B cell lymphoma. Patients with this lymphoma type have a less favorable 5-year survival rate of 31%. Although the tumors from these patients were indistinguishable histologically, they had striking differences in their gene expression profiles, as exemplified by the microarray images shown below each lymphoma subgroup. -
NIH Conflict of Interest Regs Revised
OCTOBEROCTOBER 2005 www.asbmb.org Constituent Society of FASEB AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY NIH Conflict of Interest Regs Revised SEE PAGE 30 FOR NEW CLARA BENSON TRAVEL FELLOWSHIP AWARD Held in conjunction with EB2006 Custom Antibodies Your Way! Choose the protocol that is right for you! QwikScreen ™: 65 day, 2 rabbit protocol - 4 immunizations, 3 bleeds/rabbit (~100ml serum), customer supplied peptide/protein - Options: Peptide synthesis, immunograde Conjugation to carrier u ELISA u u Animal extensionsMS analysis $685 Standard: 80 day, 2 rabbit protocol - 5 immunizations, 5 bleeds/rabbit (~ 200ml ser Options: um), ELISA, customer supplied peptide/pr Peptide synthesis MS Check™ peptide sequence confirmation u HPLC purified peptide Affinity purification otein - Pinnacle: $975 u HPLC and MS analysis u Complete Affinity Purified Protocol- Animal extensions 2 rabbit pr 5 bleeds/rabbitotocol, (~ 200mlepitope serum), design, peptide PhD technical synthesis support, (up to 20mer),5 immunizations, HPLC purified to ~85%, 5+mg peptide to customer, ELISA, evaluation period, affinity purification, and morMS Check™ peptide sequence confirmationNo Hidden Charges! e… - Discounts for Multiple Protocols$1795 , Includes peptide sequencing by CID MS/MS– u Guaranteed Peptide Let our enthusiasm for scienceExpert workTechnical for SupportFidelity! P: 508.303.8222 www.21stcenturybio.com Toll-free: 877.217.8238 F: 508.303.8333 you! E: [email protected] www.asbmb.org AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY OCTOBER -
The New Eppendorf Micro Centrifuge
The new Eppendorf Micro Centrifuge. • With 50% higher::capacity,: variable speed,. quieter operation, and .......... Brand ...: .......... Higher capacity..,plus. Safe and ru ggecJ. The new..1.8-place. Model 5415 The" Eppe~dorf 5415 Micro Micro Centrifuge g wes you Centrifuge is UL listed for ~.i.mportant operating advantages-- • . safety: It's sorugged th.atan with unique Eppendorf quality: : acci.den~tatlyiunbalanced 4oad ......... Enclosed rotor design reduces air.turbulence won't cause excessive vibration Versatile in use, and noise. Tubes are angled precisely at 45°.to 0rm0tof~ damage. M.odel.5415 has a variable-speed maximize pellet formation. For more information:: call " ' ~ : " motor that reaches a maximum 800~645-3050;. in NewYork., . of.14,000 rpm with anlRCF of 5164334.~7500.,:. Or write . 16,000 x g;. a 30-minute:timer; Brinkmann..Ins.truments, Inc., • and a momentary button for short Cantiague Road,. Westbury, spins. It accepts 1.5 mL,.500 t~L, NY 11590. (In Canada ................... 400 I~L, and 250 #L Eppendorf 416-~675W911; 50 Galaxy Blvd., •Microcentrifuge Tubes and Rexdale., Ont. M9W 4Y5) blood Collection microtubes, such as B-D Microtainer*Tubes. Specifications ......... Maximumspeed: l4,000i;pm " New rotor design. Maximum RCF ...... : 16.000 x g The enclosedrotor design Test-tube capacity ':: 1:.8 ...... reduces air turbulencefor Timerequired for " - " maximum speed i....10.sec. quieter operation:. And the new Timerequired to stop I~2 sec ........ - Quick, release feature; aitowsthe18-position :.Dimensions quick,reie.ase featu re lets.you rotor to be easily transported even.when ....... (L X W x H): 28 X 2! x 28.5 cm transport the: rotor with tubes--- Loaded ..... -
Invited Keynote Speakers, Chairs and Vice Chairs
Invited Keynote Speakers, Chairs and Vice Chairs Session 1 - Viruses: From Environments to Clinics Tuesday, June 19th, 2018 Keynote Speaker: Dr. Peter Palese, Mount Sinai, New York, USA Towards a Universal Influenza Virus Vaccine Dr. Peter Palese is a Professor of Microbiology and the Chair of the Department of Microbiology at the Icahn School of Medicine at Mount Sinai. His research is in the area of RNA-containing viruses with a special emphasis on influenza viruses. Specifically, he established the first genetic maps for influenza A, B, and C viruses, identified the function of several viral genes, and defined the mechanism of neuraminidase inhibitors (which are now FDA-approved antivirals). He was also a pioneer in the field of reverse genetics for negative strand RNA viruses, which allows the introduction of site-specific mutations into the genomes of these viruses. Chair: Dr. Keith Fowke, University of Manitoba, Winnipeg, MB Dr. Keith Fowke is Professor and Head in the Department of Medical Microbiology and Infectious Diseases, University of Manitoba. His laboratory focuses on defining cellular immune mechanisms of the control of, and resistance to, HIV infection. Current studies include understanding how to block the negative effects of HIV to restore the immune response to full capabilities and preventing HIV infections by reducing inflammation at the genital tract. Vice-Chair: Dr. Peter Pelka, University of Manitoba, Winnipeg, MB Dr. Peter Pelka is an Assistant Professor at University of Manitoba. My lab studies how a viral oncoprotein reprograms the cell in order to support virus replication. I use the human adenovirus as a model system to study how E1A reprograms the infected cell. -
Maize Genetics Cooperation Newsletter Exists for the Benefit of the Maize Community As an Informal Vehicle for Communication
MAIZE GENETICS COOPERATION NEWSLETTER 80 July 25, 2006 The data presented here are not to be used in publications without the consent of the authors. Division of Biological Sciences and Division of Plant Services University of Missouri Columbia, Missouri The Maize Genetics Executive Committee Sarah Hake, Chair, Class of 2008 Marty Sachs, Class of 2010 Patrick Schnable, Class of 2010 Mary Schaeffer (Polacco), Class of 2009 Anne Sylvester, Class of 2009 Jo Messing, Class of 2008 Ed Buckler, Class of 2007 Karen Cone, Class of 2007 Alfons Gierl, Class of 2007 Jeanne-Philippe Vielle-Calzada, Class of 2007 Jeff Bennetzen, Class of 2006 Ron Phillips, Class of 2006 Year 2007 Maize Genetics Conference Steering Committee Anne Sylvester, Chair Thomas P. Brutnell, Co-Chair Ed Buckler Mei Guo Erin Irish Steve Moose Jorge Nieto Sotelo Peter Rogowski Richard Schneeberger Marja Timmermans Ex Officio Karen Cone, Treasurer Marty Sachs Mary Schaeffer (Polacco) Trent Seigfried NOTE: The 49th Maize Meeting will be held at St. Charles, IL, March 22-25, 2007. I. FOREWORD .......................................................................................................................................................................................................................1 II. REPORTS FROM COOPERATORS............................................................................................................................................................................2 BEIJING, CHINA Effect of space on leaf cell plasmadesma in maize (Zea mays L.) -
2005 MCDB Newsletter
MCDB N e w s Molecular, Cellular, and Developmental Biology Fall 2005 Contents Eran Pichersky James Bardwell Collegiate Awarded Named HHMI Professorship............... 1 Collegiate Investigator HHMI Investigator........ 1 Professorship MCDB Associate Professor, James MCDB Professor, Bardwell, has been selected as a Eran Pichersky, Howard Hughes Medical Institute New MCDB Website...... 1 was recently investigator effective September 1, honored by being 2005. Jim will join a prestigious group Chair’s Message............ 2 named a Collegiate of about 300 HHMI investigators Professor by the serving as faculty science Spotlight........ 2 College of LS&A members at host in recognition of Eran Pichersky institutions, like Our New his truly extraordinary record of the University of Faculty............................. 3 accomplishment in research, service Michigan, which and teaching. His title will be the has a long-term Emeritus Honors.......... 4 Michael M. Martin Collegiate collaborative Professor of Molecular, Cellular and relationship with James Bardwell In Memorium.................... 4 Developmental Biology. the HHMI. New MCDB Website MCDB Faculty MCDB is pleased to announce the launching of our new departmental website Happenings..................... 4 on September 1st, 2005. We hope you will find it informative and “search friendly.” In addition to a new graphical design and greatly enhanced navigation Priscilla Connell capability, we expanded the content of the site to include new Memorial Lectures...... 5 sections such as: • Faculty News – Up-to-date information on faculty Sponsored Research happenings in MCDB. Highlights....................... 5 • People Directories – Faculty, Graduate Students, Office MC of the Chair and Staff directories featuring pictures and various sort capabilities. PostDoctoral Fellows & DB • Research – Descriptions of the six major research areas Where are they now?..